Despite the short-term effectiveness of lifestyle interventions for weight loss, many individuals regain a significant amount of weight within a 1 year period. Regular physical activity (PA) is one of the best predictors of sustained weight loss and current activity guidelines recommend high levels of PA to prevent weight regain after weight loss. However, most individuals do not achieve or sustain high levels of PA during typical weight loss programs in which diet and exercise interventions are initiated concurrently. Thus it is essential to evaluate novel strategies to promote adherence to high levels of PA within a lifestyle weight loss program. The optimal timing of exercise initiation within a weight loss program is an area that has not previously been studied. The overall objective of this proposal is to evaluate the extent to which an exercise intervention timed after diet-induced weight loss (rather than initiated concurrently) improves exercise adherence and facilitates long-term weight loss. Exercise initiation after weight loss may improve exercise adoption and adherence and promote long- term weight loss because: 1) exercise may be easier to perform at a lower body weight, 2) injury rates (and exercise attrition) may be reduced after weight loss and 3) it may be more effective to focus on a single behavior change at a time (rather than attempting concurrent changes in diet and exercise behaviors). For these reasons, we believe it may be more effective to initiate exercise after an initial period of diet-induced weight loss. Our overall hypothesis is that sequential delivery of diet and exercise interventions will result in improved weight loss at 18 months when compared to a traditional program in which identical diet and exercise interventions are initiated simultaneously. The study design involves an 18 month randomized trial within which obese subjects receive either standard behavioral therapy (Standard BT) or sequential behavioral therapy (Sequential BT). Standard BT will receive a traditional behavioral weight loss program where diet and exercise changes are initiated simultaneously. Sequential BT will receive a program that focuses solely on dietary changes in the initial 6 months, and then incorporates exercise in the ensuing 6 months. Both groups will be followed for 18 months to assess long-term weight loss. In Aim 1 we will assess the effect of timing of exercise initiatio on weight loss and body composition. In Aim 2 we will assess the effect of timing of exercise initiation on free living PA and cardio-respiratory fitness. In Aim 3 we will assess the effect of timing of exercise initiation on adherence to dietary weight control behaviors. In Aim 4 we will explore mechanisms (perception of exercise, exercise related injuries, and behavioral constructs related to our hypothesis) through which timing of exercise initiation may impact long-term weight loss. The approach is innovative as it focuses on determining the optimal time to begin exercise rather than evaluating a specific frequency, intensity, or duration of exercise. The proposed study is significant as it could identify a strategy that could aid in the development of more effective obesity treatment programs and help more people achieve and sustain a weight loss.